Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia

Carla De Angelis; Alicia B Byrne; Rebecca Morrow; Jinghua Feng; Thuong Ha; Paul Wang; Andreas W Schreiber; Milena Babic; Ajay Taranath; Nick Manton; Sarah L King-Smith; Quenten Schwarz; Peer Arts; Hamish S Scott; Christopher Barnett

doi:10.1186/s12920-021-00911-4

Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia

BMC Med Genomics. 2021 Feb 27;14(1):64. doi: 10.1186/s12920-021-00911-4.

Authors

Carla De Angelis^#^{1

2}, Alicia B Byrne^#^{3

4}, Rebecca Morrow³, Jinghua Feng^{5

4}, Thuong Ha^{3

5}, Paul Wang⁵, Andreas W Schreiber^{5

4

6}, Milena Babic³, Ajay Taranath^{7

2}, Nick Manton⁸, Sarah L King-Smith^{3

9}, Quenten Schwarz^{10

4}, Peer Arts³, Hamish S Scott^#^{3

5

2

4

9}, Christopher Barnett^#^{11

12

13}

Affiliations

¹ Paediatric and Reproductive Genetics Unit, Women's and Children's Hospital, North Adelaide, SA, Australia.
² School of Medicine, University of Adelaide, Adelaide, SA, Australia.
³ Genetics and Molecular Pathology Research Laboratory, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, Australia.
⁴ School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
⁵ ACRF Cancer Genomics Facility, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, SA, Australia.
⁶ School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
⁷ South Australian Medical Imaging, Women's and Children's Hospital, North Adelaide, SA, Australia.
⁸ Department of Surgical Pathology, Women's and Children's Hospital/SA Pathology, North Adelaide, SA, Australia.
⁹ Australian Genomic Health Alliance, Melbourne, VIC, Australia.
¹⁰ Neurovascular Research Laboratory, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, Australia.
¹¹ Paediatric and Reproductive Genetics Unit, Women's and Children's Hospital, North Adelaide, SA, Australia. [email protected].
¹² School of Medicine, University of Adelaide, Adelaide, SA, Australia. [email protected].
¹³ SA Clinical Genetics Service, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA, 5006, Australia. [email protected].

^# Contributed equally.

Abstract

Background: Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH.

Case presentation: We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus.

Conclusion: We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.

Keywords: Case report; LAMC3; Lobe; Occipital; Periventricular nodular heterotopia.

Publication types

Case Reports
Research Support, N.I.H., Extramural

MeSH terms

Adult
Female
Heterozygote
Humans
Mutation
Periventricular Nodular Heterotopia* / diagnostic imaging
Periventricular Nodular Heterotopia* / genetics
Pregnancy

Grants and funding

UM1 HG008900/HG/NHGRI NIH HHS/United States